This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Glial cells play a key role in the assembly and function of neuronal ciruits. However, the signals exchanged by glial cells and neurons are incompletely understood. Increasing evidence supports the notion that ephrins and Eph receptors play a central role in the communication between glial cells and neuronal axons as well as dendrites in different parts of the central and peripheral nervous system. We previously described a repulsive interaction that regulates postsynaptic morphology through the EphA4 receptor tyrosine kinase and its ligand, ephrin-A3. EphA4 is enriched on dendritic spines of pyramidal neurons in the adult mouse hippocampus and ephrin-A3 is localized on astrocytic processes that face synapses. We found that activation of EphA4 by ephrin-A3 induces dendritic spine retraction, whereas decreased EphA4-ephrin interaction distorts dendritic spine shape and organization.